Conantokin-G (P01338) Protein Card

General Information

Name	Conantokin-G
Alternative name(s)	CGX-1007,Con-G,sleeper
Organism	Conus geographus (Geography cone)
Organism region	Indo-Pacific
Organism diet	piscivorous
Protein Type	Wild type
Protein precursor	Conantokin-G precursor (variant) (1353) Conantokin-G precursor (1373)
Notes	Conantokin-G is active against the NMDA glutamate receptors, and more precisely a NR2B-selective competitive antagonist (Donevan and McCabe 2000). Dutt et al., 2019 reported that conantokin-G (1 μM) showed no effect on the zebrafish larvae.

Classification

Conopeptide class	conantokin
Gene superfamily	B1 superfamily
Pharmacological family

Sequence

GE(Gla)(Gla)LQ(Gla)NQ(Gla)LIR(Gla)KSN(nh2)
Modified residues	position symbol name 3 Gla Gamma carboxylic glutamic acid 4 Gla Gamma carboxylic glutamic acid 7 Gla Gamma carboxylic glutamic acid 10 Gla Gamma carboxylic glutamic acid 14 Gla Gamma carboxylic glutamic acid 18 nh2 C-term amidation
Sequence evidence	protein level
Average Mass	2264.21
Monoisotopic Mass	2262.94
Isoelectric Point	2.02
Extinction Coefficient [280nm]	NA

Activity

IC50: Ionotropic glutamate receptors

Target	Organism	IC50		Agonist	Ref
GluN2A	R. norvegicus	>10uM		200uM glutamate	Teichert,R.W. et al. (2007)
GluN2B	R. norvegicus	0.1uM		200uM glutamate	Teichert,R.W. et al. (2007)
GluN2C	R. norvegicus	1uM		200uM glutamate	Teichert,R.W. et al. (2007)
GluN2D	R. norvegicus	1uM		200uM glutamate	Teichert,R.W. et al. (2007)

Synthetic variants

Conantokin-G[+10Gla,Gla10Buc,Gla14Buc]	GE(Gla)(Gla)LQ(Gla)NQ(Gla)(Buc)LIR(Buc)KSN(nh2)
Conantokin-G[Gla10Bsc,Gla14Bsc]	GE(Gla)(Gla)LQ(Gla)NQ(Bsc)LIR(Bsc)KSN(nh2)
Conantokin-G[Gla10Buc,Gla14Buc]	GE(Gla)(Gla)LQ(Gla)NQ(Buc)LIR(Buc)KSN(nh2)
Conantokin-G[Gla7Buc,Gla14Buc]	GE(Gla)(Gla)LQ(Huc)NQ(Gla)LIR(Buc)KSN(nh2)
conantokin-G[+10O]	GE(Gla)(Gla)LQ(Gla)NQO(Gla)LIR(Gla)KSN(nh2)

References

Malmberg,A.B., Gilbert,H., McCabe,R.T. and Basbaum,A.I. (2003) Powerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and T Pain 101:109-116

Skjaerbaek,N., Nielsen,K.J., Lewis,R.J., Alewood,P. and Craik,D.J. (1997) Determination of the solution structures of conantokin-G and conantokin-T by CD and NMR spectroscopy J. Biol. Chem. 272:2291-2299

Rigby,A.C., Baleja,J.D., Furie,B.C. and Furie,B. (1997) Three-dimensional structure of a gamma-carboxyglutamic acid-containing conotoxin, conantokin G, from the marine snail Conus geographus: the metal-free conformer Biochemistry 36:6906-6914

Rigby,A.C., Baleja,J.D., Li,L., Pedersen,L.G., Furie,B.C. and Furie,B. (1997) Role of gamma-carboxyglutamic acid in the calcium-induced structural transition of conantokin G, a conotoxin from the marine snail Conus geographus Biochemistry 36:15677-15684

McIntosh,J.M., Olivera,B.M., Cruz,L.J. and Gray,W.R. (1984) Gamma-carboxyglutamate in a neuroactive toxin J. Biol. Chem. 259:14343-14346

Williams,A.J., Dave,J.R., Phillips,J.B., Lin,Y. and Tortella,F.C. (2000) Neuroprotective efficacy and therapeutic window of the high-affinity N-methyl-D-aspartate antagonist conantokin-G: in vitro (primary cerebellar neurons) and in vivo (rat model of transient focal brain ischemia) studies. J. Pharmacol. Exp. Ther. 294:378-386

Williams,A.J., Ling,G. and Tortella,F.C. (2002) Intrathecal CGX-1007 is neuroprotective in a rat model of focal cerebral ischemia. Neuroreport 13:821-824

Williams,A.J., Ling,G., Berti,R., Moffett,J.R., Yao,C., Lu,X.M. and Tortella,F.C. (2003) Treatment with the snail peptide CGX-1007 reduces DNA damage and alters gene expression of c-fos and bcl-2 following focal ischemic brain injury in rats. Exp Brain Res 153:16-26

Donevan,S.D. and McCabe,R.T. (2000) Conantokin G is an NR2B-selective competitive antagonist of N-methyl-D-aspartate receptors. Mol. Pharmacol. 58:614-623

Olivera BM, McIntosh JM, Clark C, Middlemas D, Gray WR, Cruz LJ. (1985) A sleep-inducing peptide from Conus geographus venom. Toxicon 23:277-282

Balsara,R., Li,N., Weber-Adrian,D., Huang,L. and Castellino,F.J. (2012) Opposing action of conantokin-G on synaptically and extrasynaptically-activated NMDA receptors. Neuropharmacology 62:2227-2238

Dutt,M., Giacomotto,J., Ragnarsson,L., Andersson,Å., Brust,A., Dekan,Z., Alewood,P.F., and Lewis,R.J. (2019) The α1-adrenoceptor inhibitor ρ-TIA facilitates net hunting in piscivorous Conus tulipa Scientific reports 9:17841

Internal links

Protein Precursor	Conantokin-G precursor (variant) (1353) Conantokin-G precursor (1373)
Nucleic acids
Structure	NMR STRUCTURE OF METAL-FREE CONANTOKIN G, 1 STRUCTURE NMDA RECEPTOR ANTAGONIST, CONANTOKIN-G, NMR, 17 STRUCTURES NMR STRUCTURE OF CALCIUM BOUND CONFORMER OF CONANTOKIN G, MINIMIZED AVERAGE STRUCTURE The Solution Structure of the Magnesium-bound Conantokin-G

External links

Ncbi	1AD7_A, 1AWY_A, 1ONU_A

Tools

Please cite:
Kaas Q, Yu R, Jin AH, Dutertre S and Craik DJ. ConoServer: updated content, knowledge, and discovery tools in the conopeptide database. Nucleic Acids Research (2012) 40(Database issue):D325-30
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6

ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia.

The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David Craik (d.craik@imb.uq.edu.au).

Contacts:
David Craik
Quentin Kaas

Last updated: Friday 1 December 2023